Antiemetic effects of baclofen in a shrew model of postoperative nausea and vomiting: Whole-transcriptome analysis in the nucleus of the solitary tract

Aims: The molecular genetic mechanisms underlying postoperative nausea and vomiting (PONV) in the brain have not been fully elucidated. This study aimed to determine the changes in whole transcriptome in the nucleus of the solitary tract (NTS) in an animal model of PONV, to screen a drug candidate and to elucidate the molecular genetic mechanisms of PONV development. Methods: Twenty-one female musk shrews were assigned into three groups: the Surgery group (shrew PONV model, n = 9), the Sham group (n = 6), and the Naïve group (n = 6). In behavioral studies, the main outcome was the number of emetic episodes. In genetic experiments, changes in the transcriptome in the NTS were measured. In a separate study, 12 shrews were used to verify the candidate mechanism underlying PONV. Results: A median of six emetic episodes occurred in both the Sham and Surgery groups. Whole-transcriptome analysis indicated the inhibition of the GABA_B receptor-mediated signaling pathway in the PONV model. Baclofen (GABA_B receptor agonist) administration eliminated emetic behaviors in the shrew PONV model. Conclusions: Our findings suggest that the GABA_B receptor-mediated signaling pathway is involved in emesis and that baclofen may be a novel therapeutic or prophylactic agent for PONV.